Chai Hong, Yan Shaoyu, Lin Peter, Lumsden Alan B, Yao Qizhi, Chen Changyi
Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
J Am Coll Surg. 2005 Jun;200(6):820-30. doi: 10.1016/j.jamcollsurg.2005.02.030.
HIV protease inhibitor ritonavir (RTV) is associated with many cardiovascular complications and causes vascular dysfunction through oxidative stress. In the present study, we determined the effects of RTV and curcumin (a pigment derived from turmeric) on porcine coronary arteries.
Artery rings were incubated with 15 microM concentration of RTV and curcumin (5 or 10 microM) for 24 hours. Vasomotor function was studied with a myograph tension system. Endothelial nitric oxide synthase (eNOS) mRNA and protein levels were studied using real-time polymerase chain reaction, Western blot, and immunohistochemistry. Nitric oxide was measured using Griess assay. Superoxide anion levels were determined by lucigenin enhanced chemiluminescence.
RTV considerably reduced vessel contraction by 71%, endothelium-dependent relaxation by 59%, and endothelium-independent relaxation by 52%, as compared with controls. Curcumin effectively blocked RTV-induced vasomotor dysfunction. RTV-treated arteries showed substantial reductions of eNOS mRNA by 77%, eNOS protein by 72%, and nitric oxide release by 37% as compared with controls. The RTV plus curcumin-treated vessels showed substantial increases of eNOS and nitric oxide levels as compared with the RTV-treated vessels. Finally, there was a 47% increase of superoxide anion production in the RTV-treated vessels as compared with controls. Again, curcumin effectively reversed this effect of RTV.
HIV protease inhibitor RTV impairs vasomotor functions, reduces eNOS expression and nitric oxide release, and increases oxidative stress in porcine coronary arteries. Curcumin effectively blocks these detrimental effects of RTV.
HIV蛋白酶抑制剂利托那韦（RTV）与许多心血管并发症相关，并通过氧化应激导致血管功能障碍。在本研究中，我们确定了RTV和姜黄素（一种从姜黄中提取的色素）对猪冠状动脉的影响。
将动脉环与15微摩尔浓度的RTV和姜黄素（5或10微摩尔）一起孵育24小时。使用肌动描记张力系统研究血管舒缩功能。使用实时聚合酶链反应、蛋白质印迹和免疫组织化学研究内皮型一氧化氮合酶（eNOS）的mRNA和蛋白质水平。使用格里斯试剂法测量一氧化氮。通过光泽精增强化学发光法测定超氧阴离子水平。
与对照组相比，RTV使血管收缩显著降低71%，内皮依赖性舒张降低59%，非内皮依赖性舒张降低52%。姜黄素有效阻断了RTV诱导的血管舒缩功能障碍。与对照组相比，经RTV处理的动脉中eNOS mRNA显著降低77%，eNOS蛋白降低72%，一氧化氮释放降低37%。与经RTV处理的血管相比，经RTV加姜黄素处理的血管中eNOS和一氧化氮水平显著升高。最后，与对照组相比，经RTV处理的血管中超氧阴离子产生增加了47%。同样，姜黄素有效逆转了RTV的这种作用。
HIV蛋白酶抑制剂RTV损害猪冠状动脉的血管舒缩功能，降低eNOS表达和一氧化氮释放，并增加氧化应激。姜黄素有效阻断RTV的这些有害作用。
